The Alzheimer's Disease Research Center (ADRC) Neuropathology Core has been completely reorganized during the present grant period. It provides state-of-the-art neuropathological examination of brains obtained from ADRC autopsy cases. Brains are processed in a standardized fashion, with detailed histopathological assessment, by means of examination of a standardized set of brain sections, now illustrated on our website. Standardized reports with extensive data are provided, including histopathological diagnoses using accepted neuropathological criteria and CERAD, NLA-Reagan, and Braak &Braak staging systems. The new procedures enhance the efficiency of the ADRC brain bank, and the value of collected brains to investigators whose specific research projects depend upon the availability of carefully prepared and examined tissue. Each ADRC brain is bisected, with one half formalin-fixed, and thoroughly examined neuropathologically. The other half is extensively dissected yielding up to 150 or more fresh frozen samples from precisely specified regions, harvested and processed at time of autopsy. Only trained neuropathologists perform the dissection to ensure consistency and accurate assessment of the tissue during the processing. The samples are categorized both diagnostically and qualitatively, electronically-tracked, ready for instant disbursement, and suitable for a wide range of investigations using various modern biochemical technologies. In addition to managing the collections of fresh frozen, and formalin-fixed brain samples, DNA and RNA samples are prepared and then stored from frozen brains, as is DNA from blood of living ADRC patients. The voluminous nature of the Neuropathology Core samples requires recording many crucial details. Thus, we have developed software that: (i) generates bar-code labels and tracks samples;(ii) pre-selects among thousand of samples those that best match the requirements of investigators according to the demographics and pathological changes;(iii) provides freezer cabinet coordinates for each sample;(iv) traces vacant freezer space after sample disbursements;and (v) registers recipient investigators. The Neuropathology Core actively supports numerous fertile interactions between neuroscientists, geneticists, clinicians and other AD researchers.